We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks post-surgery, a cohort of mice with established HF (% ejection fraction; %EF<45) was administered resveratrol (~450 mg/kg/d) or vehicle for 2 weeks. Although %EF was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch towards greater whole-body glucose utilization and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O2 consumption in isolated skeletal muscle fibers compared to sham mice, which was completely normalized by resveratrol treatment. Resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Overall, our pre-clinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients.
- heart failure
- exercise intolerance
- oxidative capacity
- gut microbiome
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology